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Maternal allopurinol administration during suspected fetal hypoxia: a novel neuroprotective intervention? A multicentre randomised placebo controlled trial
  1. Joepe J Kaandorp1,
  2. Manon J N L Benders1,
  3. Ewoud Schuit2,
  4. Carin M A Rademaker3,
  5. Martijn A Oudijk1,
  6. Martina M Porath4,
  7. Sidarto Bambang Oetomo4,
  8. Maurice G A J Wouters5,
  9. Ruurd M van Elburg5,6,
  10. Maureen T M Franssen7,
  11. Arie F Bos7,
  12. Timo R de Haan8,
  13. Janine Boon9,
  14. Inge P de Boer9,
  15. Robbert J P Rijnders10,
  16. Corrie J W F M Jacobs10,
  17. Liesbeth H C J Scheepers11,
  18. Danilo A W Gavilanes11,
  19. Kitty W M Bloemenkamp12,
  20. Monique Rijken12,
  21. Claudia A van Meir13,
  22. Jeannette S von Lindern13,
  23. Anjoke J M Huisjes14,
  24. Saskia C M J E R Bakker14,
  25. Ben W J Mol7,
  26. Gerard H A Visser1,
  27. Frank Van Bel1,
  28. Jan B Derks1
  1. 1Department of Perinatology, University Medical Center, Utrecht, The Netherlands
  2. 2Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands
  3. 3Department of Clinical Pharmacy, University Medical Center, Utrecht, The Netherlands
  4. 4Department of Perinatology, Maxima Medical Center, Veldhoven, The Netherlands
  5. 5Department of Perinatology, VU Medical Center, Amsterdam, The Netherlands
  6. 6Danone Research, Wageningen, The Netherlands
  7. 7Department of Perinatology, University Medical Center, Groningen, The Netherlands
  8. 8Department of Perinatology, Academic Medical Center, Amsterdam, The Netherlands
  9. 9Department of Perinatology, Diakonessenhuis, Utrecht, The Netherlands
  10. 10Department of Perinatology, Jeroen Bosch Medical Center, Den Bosch, The Netherlands
  11. 11Department of Perinatology, Maastricht University Medical Center, Maastricht, The Netherlands
  12. 12Department of Perinatology, Leids University Medical Center, Leiden, The Netherlands
  13. 13Department of Perinatology, Groene Hart Hospital, Gouda, The Netherlands
  14. 14Department of Perinatology, Gelre Hospitals, Apeldoorn, The Netherlands
  1. Correspondence to Dr Joepe J Kaandorp, University Medical Center Utrecht, Room 04.123.1, PO Box 85090, Utrecht 3508 AB, The Netherlands; j.j.kaandorp{at}, j.j.kaandorp{at}


Objective To determine whether maternal allopurinol treatment during suspected fetal hypoxia would reduce the release of biomarkers associated with neonatal brain damage.

Design A randomised double-blind placebo controlled multicentre trial.

Patients We studied women in labour at term with clinical indices of fetal hypoxia, prompting immediate delivery.

Setting Delivery rooms of 11 Dutch hospitals.

Intervention When immediate delivery was foreseen based on suspected fetal hypoxia, women were allocated to receive allopurinol 500 mg intravenous (ALLO) or placebo intravenous (CONT).

Main outcome measures Primary endpoint was the difference in cord S100ß, a tissue-specific biomarker for brain damage.

Results 222 women were randomised to receive allopurinol (ALLO, n=111) or placebo (CONT, n=111). Cord S100ß was not significantly different between the two groups: 44.5 pg/mL (IQR 20.2–71.4) in the ALLO group versus 54.9 pg/mL (IQR 26.8–94.7) in the CONT group (difference in median −7.69 (95% CI −24.9 to 9.52)). Post hoc subgroup analysis showed a potential treatment effect of allopurinol on the proportion of infants with a cord S100ß value above the 75th percentile in girls (ALLO n=5 (12%) vs CONT n=10 (31%); risk ratio (RR) 0.37 (95% CI 0.14 to 0.99)) but not in boys (ALLO n=18 (32%) vs CONT n=15 (25%); RR 1.4 (95% CI 0.84 to 2.3)). Also, cord neuroketal levels were significantly lower in girls treated with allopurinol as compared with placebo treated girls: 18.0 pg/mL (95% CI 12.1 to 26.9) in the ALLO group versus 32.2 pg/mL (95% CI 22.7 to 45.7) in the CONT group (geometric mean difference −16.4 (95% CI −24.6 to −1.64)).

Conclusions Maternal treatment with allopurinol during fetal hypoxia did not significantly lower neuronal damage markers in cord blood. Post hoc analysis revealed a potential beneficial treatment effect in girls.

Trial registration number NCT00189007, Dutch Trial Register NTR1383.

  • Allopurinol
  • Fetal asphyxia
  • Neuroprotection
  • S100B
  • Gender difference

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